The binding of phosphatidylglycerol liposomes to rat platelets is mediated by complement.
Previous work has shown that intravenous administration of phosphatidylglycercol (PG) containing liposomes to rats results in a rapid transient decline in platelet count (1). Here the interactions of PG liposomes with rat platelets in vitro have been examined with the aim of characterizing factors associated with the decline. It is shown that PG liposomes induce formation of rat (but not human) platelet-liposome microaggregates in vitro. The PG liposome dependent thrombocytopenia observed in vivo can therefore be attributed to sequestration of PG liposome-platelet aggregates. Further, the aggregation of platelets with PG liposomes, which can be monitored as a reduction in platelet count using a coulter counter, is shown to be mediated by a serum complement factor, likely C3b. This is indicated by a requirement of plasma for the in vitro reduction in platelet count induced by PG liposomes, and the inhibition of this effect by heat treatment of plasma, by incubation of plasma with purified cobra venom factor, or by removal of C3 from plasma.
Loughrey
H C
HC
University of British Columbia, Faculty of Medicine, Department of Biochemistry, Vancouver, Canada.
Bally
M B
MB
Reinish
L W
LW
Cullis
P R
PR
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D015153:Blotting, Western; D003176:Complement C3 / Q000502:physiology*; D004337:Drug Carriers; D004591:Electrophoresis, Polyacrylamide Gel; D008081:Liposomes; D008858:Microscopy, Phase-Contrast; D010715:Phosphatidylglycerols / Q000008:administration & dosage / Q000097:blood*; D010976:Platelet Count / Q000187:drug effects; D051381:Rats
D003176:Complement C3; D004337:Drug Carriers; D008081:Liposomes; D010715:Phosphatidylglycerols